The overall goal ofthis application is to continue operation ofthe National Swine Resource and Research Center (NSRRC). To date, the NSRRC is just beginning its ninth year of operation and it has successfully developed the infrastructure needed to assist swine-based research across multiple disciplines. Functionally, the NSRRC has been actively engaged in recruiting and importing swine models into the Center and in distributing cells, tissues, organs and pigs to investigators throughout the United States and Europe. The NSRRC also provides invaluable services to the research community by creating new genetically-engineered swine models needed by investigators and by training and educating scientists regarding the use of swine in biomedical research. Importantly, we have built an entirely new National Swine Resource and Research Center building, with state-of-the-art high biosecurity, to house the functions ofthe NSRRC. The Specific Aims for the upcoming grant period are as follows: 1. To operate the National Swine Research and Resource Center. Functions of the NSRRC will continue to include: a) importation of existing swine models of human health and disease, b) rederivation of pigs to eliminate specific pathogens, and health monitoring to assure maintenance of a specific pathogen-free status, c) cryopreservation and storage of gametes, embryos and somatic cells to prevent future loss of valuable models, d) distribution of reagents, cells, tissues, organs and pathogen-free pigs, and e) creation of new genetically-engineered pigs needed by the biomedical research community. 2. To perform innovative research that will benefit the NSRRC and the biomedical research community. Applied research projects are aimed at improving: a) the cryopreservation of pig reproductive cells and tissues, b) developing state-of-the-art testing methods for swine health surveillance, and c) the development of improved methods for the production of genetically-engineered pigs. The NSRRC will also serve as a site for training and educational activities related to research employing swine models. RELEVANCE (See instructions): The National Swine Resource and Research Center will continue to curate and provide much needed swine genetics that will be used to test treatments and therapies for human diseases. The National Swine Resource and Research Center will also create and distribute genetically engineered swine that manifest human diseases or can be used to treat human diseases.